Multimodal Ocular Imaging in Neurodegeneration

Completed

• Conditions: Alzheimer Disease; Alzheimer Dementia; Frontotemporal Dementia
• Interventions: Device: Spectral-Domain Optical Coherence Tomography (SD-OCT); Device: Magnetic Resonance Imaging (MRI); Device: Positron Emission Tomography (PET); Diagnostic Test: Comprehensive Ophthalmic Examination; Device: Fundus Photography

• Registration Number: NCT03699644
• Lead Sponsor: University of Michigan

Brief Summary

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two of the most common types of age-related neurodegenerative disorders. Identifying at-risk patients and gauging disease progression in a non-invasive manner would be invaluable. Early and correct diagnosis is crucial for coordinating supportive care, patient expectations, caregiver arrangements and family planning. In addition, as treatments become available, beginning therapy early in the disease before symptoms become severe will be important. Multimodal ocular imaging (MOI) includes an ophthalmic (eye) exam and eye photographs to evaluate different layers of the retina, which is the light sensing layer of the eye. Newer technologies make it possible to visualize the disease process occurring in AD and FTD by using MOI to look at the retina, since the retina is fundamentally an outward extension of the brain itself. This study will attempt to correlate signs of disease in the retina, as determined by MOI, with plaque buildup in the brain as seen by imaging. This will demonstrate the sensitivity and specificity of MOI for diagnosing AD and FTD in a noninvasive manner.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-05
• Study First Submitted QC: 2018-10-05
• Study First Posted: 2018-10-09
• Study Start: 2019-01-04
• Primary Completion: 2019-04-03
• Study Completion: 2019-04-03
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-10
• Last Update Posted: 2022-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Subjects with dementia must have known diagnosis of Alzheimer's dementia (AD) or frontotemporal dementia (FTD)
• Subjects with dementia must have Moderate/severe dementia as preferentially defined by a documented MoCA score of less than 17, or by MMSE score of less than 17, within the last 12 months
• Individuals with no evidence of AD or FTD as age-matched controls.

Read More

Exclusion Criteria

• Preexisting retinal or optic nerve disorder including macular degeneration, diabetic retinopathy, retinal dystrophy, and glaucoma
• Anterior segment abnormalities of the eye limiting ocular imaging (e.g. corneal disorders, dense cataract).
• Use of medications with known effects on the retina or optic nerve (e.g. hydroxychloroquine, ethambutol).
• Pregnant or lactating women.
• Prisoners.
• Subjects with advanced dementia who cannot be independently and reliably positioned at the ocular imaging device for reliable imaging.
• Subjects with contraindications to magnetic resonance (MR) imaging, including pacemakers or claustrophobia.
• Evidence of large vessel stroke or mass lesion identified on MR imaging.
• Subjects limited by participation in research procedures involving ionizing radiation.
• Subjects who are already participating in another clinical study or clinical trial
• Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of any of the investigators, might preclude safe completion of the study or might affect the results of the study. These include conditions causing significant central nervous system or autonomic dysfunction, such as congestive heart failure, recent (<6 months) myocardial infarction, thrombocytopenia (<50 x 10(9)/L), immunosuppressed state, severe uncontrolled hypertension, severe cardiopulmonary disease, severe anemia (hemoglobin <8g/dl), severe liver or kidney disease (creatinine >2.3 mg/dl) uncontrolled diabetes mellitus (HgbA1c >10g%), alcoholism, malignant neoplasms, amyloidosis, uncontrolled hypothyroidism, unstable peripheral neuropathies, concurrent infections, orthopedic problems that compromise mobility and activities of daily living, severe cerebrovascular accidents (causing symptoms such as hemiplegia, aphasia and non-dominant parietal lobe syndrome), history of exposure to neurotoxins or neuroactive drugs, or parkinsonism due to drugs (including neuroleptics, alpha-methyldopa, reserpine, metoclopramide).

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Control	Magnetic Resonance Imaging (MRI)	Healthy controls will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all healthy controls will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Alzheimer's Dementia	Fundus Photography	Subjects with Alzheimer's Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all subjects with Alzheimer's Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Healthy Control	Spectral-Domain Optical Coherence Tomography (SD-OCT)	Healthy controls will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all healthy controls will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Alzheimer's Dementia	Spectral-Domain Optical Coherence Tomography (SD-OCT)	Subjects with Alzheimer's Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all subjects with Alzheimer's Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Alzheimer's Dementia	Comprehensive Ophthalmic Examination	Subjects with Alzheimer's Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all subjects with Alzheimer's Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Healthy Control	Positron Emission Tomography (PET)	Healthy controls will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all healthy controls will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Alzheimer's Dementia	Positron Emission Tomography (PET)	Subjects with Alzheimer's Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all subjects with Alzheimer's Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Frontotemporal Dementia	Positron Emission Tomography (PET)	Subjects with Frontotemporal Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, subjects with Frontotemporal Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Frontotemporal Dementia	Fundus Photography	Subjects with Frontotemporal Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, subjects with Frontotemporal Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Frontotemporal Dementia	Spectral-Domain Optical Coherence Tomography (SD-OCT)	Subjects with Frontotemporal Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, subjects with Frontotemporal Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Healthy Control	Comprehensive Ophthalmic Examination	Healthy controls will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all healthy controls will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Healthy Control	Fundus Photography	Healthy controls will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all healthy controls will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Alzheimer's Dementia	Magnetic Resonance Imaging (MRI)	Subjects with Alzheimer's Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, all subjects with Alzheimer's Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Frontotemporal Dementia	Comprehensive Ophthalmic Examination	Subjects with Frontotemporal Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, subjects with Frontotemporal Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.
Frontotemporal Dementia	Magnetic Resonance Imaging (MRI)	Subjects with Frontotemporal Dementia will undergo a single magnetic resonance imaging (MRI) and PET (positron emission tomography) scan of the brain. In addition, subjects with Frontotemporal Dementia will receive a comprehensive ophthalmic examination as well as undergo photography and imaging of the eye.

Primary Outcome Measures

Name	Time	Method
Presence of Retinal Thinning	45 minutes	Imaging of the eye will be used to measure differences in retinal thickness between subjects with Alzheimer's Dementia, Frontotemporal Dementia, and healthy age-matched controls.

Secondary Outcome Measures

Name	Time	Method
Presence of Brain Metabolism	180 Minutes	PET scanning of the brain will be performed in order to determine if brain metabolism observed on neuroimaging correlates quantitatively and/or qualitatively with retinal thickness.
Presence of Amyloid Plaque	45 Minutes	Fundus autofluorescence (FAF) will be used to detect the presence of lipofuscin
Presence of Brain Pathology	60 Minutes	MRI of the brain will be performed in order to determine if pathology observed on neuroimaging correlates quantitatively and/or qualitatively with retinal thickness.
Presence of Macular Vascular Anomalies	45 Minutes	Imaging of the eye will be used to measure differences in vascular density between subjects with Alzheimer's Dementia, Frontotemporal Dementia, and healthy age-matched controls.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States